Adjuvant hormonal therapy: Longer duration is better to treat prostate cancer

Chicago-Among men with unfavorable prostate cancer being treated with radiotherapy and adjuvant androgen suppression, there appear to be significant outcomes advantages for a prolonged duration (>6 years) of hormonal therapy, according to a secondary analysis of data from a phase III Radiation Therapy Oncology Group (RTOG) trial.

The effect of duration of adjuvant hormonal therapy on a variety of endpoints was investigated using data collected in RTOG 85-31, a trial that was designed to investigate the benefit of androgen suppression as an adjuvant to radiotherapy. RTOG 85-31 enrolled 977 men who were randomized to receive pelvic radiotherapy (60-66 Gy) with or without hormonal therapy. According to the protocol, men randomized to adjuvant hormonal therapy were to continue treatment for life with monthly injections of goserelin acetate (Zoladex), 3.6 mg. However, the majority of patients voluntarily discontinued hormonal therapy before experiencing disease progression.

Considering 377 analyzable patients who were alive with no evidence of disease while still on hormonal therapy or at the time it was stopped, the median duration of treatment was 3.59 years. Approximately two-thirds of the men were treated for 6 years or less and one-third were treated for longer than 6 years.

"The results of this secondary analysis provide some food for thought considering current trends toward administering HT for a shorter duration," said first author Luis Souhami, MD, professor of radiation oncology at McGill University, Montreal. "While our findings can be considered only as hypothesis-generating, they suggest that approaches shortening the HT duration may be the wrong strategy. Perhaps we should be looking at HT from the other direction, just as in breast cancer, where the recommended duration for tamoxifen has been extended to 5 years."

Weighing the results

Discussing this report, Glenn J. Bubley, MD, director of genitourinary oncology at Beth Israel Deaconess Hospital in Boston, described it as a "fascinating re-analysis."

"It has been documented many times that HT as an adjuvant to radiotherapy provides a survival benefit. However, the optimal duration of HT is not known. These results from an investigation of HT duration are not what I would like to see considering the patients I treat with HT would prefer to stay on it for a shorter time," Dr. Bubley said.

"RTOG 85-31 was not originally powered for this type of analysis, and the number of men in some of the HT duration groups was small," he added. "Nevertheless, we need to wonder if we are treating for too short of a time when using HT as an adjuvant to radiotherapy."

Two prospective trials are comparing adjuvant hormonal therapy administered for 3 years versus a shorter period. A randomized European Organisation for Research and Treatment of Cancer trial (22961) reported by Michel Bolla, MD, at the ASCO meeting showed 6 months of treatment was inferior to 36 months of treatment. The other trial is an ongoing study in Quebec that is comparing 18 months and 36 months of hormonal therapy. The Quebec trial is accruing well and is expected to close by February 2008, Dr. Souhami noted.

Men were eligible for enrollment in RTOG 85-31 if they had clinical stage T3 or pN+ disease or were found on prostatectomy to have capsular penetration, positive margins, or seminal vesicle invasion. Between 1987 and 1992, 500 men were randomized to receive pelvic radiotherapy (60-66 Gy) alone and 477 men were randomized into the combination treatment group. Published results from the study showed adjuvant hormonal therapy had significant benefits for improving overall survival, disease-specific mortality, and both local and distant disease control (Int J Radiat Oncol Biol Phys 2005; 61:1285-90).

"One thing to keep in mind when interpreting the results of our secondary analysis is that this trial was begun in an era preceding PSA testing, and therefore the participants likely represent a very unfavorable group of prostate cancer patients," Dr. Souhami told Urology Times.